TY - JOUR
T1 - A selective requirement for copper-dependent activation of cytochrome c oxidase by Cox17p
AU - Kako, Koichiro
AU - Takehara, Akio
AU - Arai, Hidenori
AU - Onodera, Takashi
AU - Takahashi, Yoshinori
AU - Hanagata, Hiroshi
AU - Ogra, Yasumitsu
AU - Takagi, Hiroaki
AU - Kodama, Hiroko
AU - Suzuki, Kazuo T.
AU - Munekata, Eisuke
AU - Fukamizu, Akiyoshi
PY - 2004/11/26
Y1 - 2004/11/26
N2 - Cox17p is cloned from yeast as a chaperone to deliver copper to the mitochondria of assembly for cytochrome c oxidase (CCO). In mammals, CCO is a key enzyme for cellular respiration and a defect in its function is associated with severe neonatal or infantile lactic acidosis and early death. Recently, we found that Cox17p is not only required for mitochondrial oxidative phosphorylation but also is essential for embryonic growth and development in COX17 gene-deficient mice. To investigate its biochemical features, recombinant human Cox17p was overexpressed and purified without a purification tag. It specifically binds Cu(I) at a molar copper content of 3.3 ± 0.04 under reduced conditions and significantly activates the mitochondrial CCO in vitro. Although the Cu-Cox17p complex was maintained between pH values from 5.0 to 7.7, Cu was completely released from Cox17p at pH 8.0. An acute exposure of excess amount of copper ion to mouse cells resulted in a significant reduction of Cox17p mRNA expression, whereas copper starvation maintained the Cox17p transcription level. These results suggest that the stringent selectivity of Cox17p for copper is required for CCO activation, to prevent copper overload, or promote the supply of copper.
AB - Cox17p is cloned from yeast as a chaperone to deliver copper to the mitochondria of assembly for cytochrome c oxidase (CCO). In mammals, CCO is a key enzyme for cellular respiration and a defect in its function is associated with severe neonatal or infantile lactic acidosis and early death. Recently, we found that Cox17p is not only required for mitochondrial oxidative phosphorylation but also is essential for embryonic growth and development in COX17 gene-deficient mice. To investigate its biochemical features, recombinant human Cox17p was overexpressed and purified without a purification tag. It specifically binds Cu(I) at a molar copper content of 3.3 ± 0.04 under reduced conditions and significantly activates the mitochondrial CCO in vitro. Although the Cu-Cox17p complex was maintained between pH values from 5.0 to 7.7, Cu was completely released from Cox17p at pH 8.0. An acute exposure of excess amount of copper ion to mouse cells resulted in a significant reduction of Cox17p mRNA expression, whereas copper starvation maintained the Cox17p transcription level. These results suggest that the stringent selectivity of Cox17p for copper is required for CCO activation, to prevent copper overload, or promote the supply of copper.
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U2 - 10.1016/j.bbrc.2004.09.211
DO - 10.1016/j.bbrc.2004.09.211
M3 - Article
C2 - 15504366
AN - SCOPUS:14344264598
SN - 0006-291X
VL - 324
SP - 1379
EP - 1385
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -